Three polymorphisms in cytochrome P450 1B1 (CYP1B1) gene and breast cancer risk: A meta-analysis

Cytochrome P450 1B1 (CYP1B1) is a P450 enzyme implicated in the metabolism of exogenous and endogenous substrates. The metabolism of polycyclic aromatic hydrocarbons and other procarcinogens through CYP1B1 may well lead to their activation. Apart from the extensively studied Val432Leu polymorphism, three single nucleotide polymorphisms in CYP1B1 have been studied concerning their potential implication in terms of breast cancer risk: Arg48Gly, Ala119Ser and Asn453Ser. This meta-analysis aims to examine whether the three aforementioned polymorphisms are associated with breast cancer risk. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to December 2009. Concerning Arg48Gly polymorphism, 10 studies were eligible (11,321 cases and 13,379 controls); 11 studies were eligible for Ala119Ser (10,715 cases and 11,678 controls); 12 cases were eligible regarding Asn453Ser (11,630 cases and 14,053 controls). Pooled odds ratios (OR) were appropriately derived form fixed-effects or random-effects models. Sensitivity analysis excluding studies whose genotype frequencies in controls significantly deviated from Hardy-Weinberg equilibrium was performed. Concerning Arg48Gly, the pooled ORs (95% CI) were 0.933 (0.808-1.078) for heterozygous and 0.819 (0.610-1.100) for homozygous Gly subjects. Regarding Ala119Ser, the pooled ORs were 0.992 (0.896- 1.097) for heterozygous and 0.935 (0.729-1.198) for homozygous Ser subjects. With respect to Asn453Ser, the pooled ORs were 0.961 (0.906-1.019) for heterozygous and 0.984 (0.846-1.144) for homozygous Ser subjects. In conclusion, this meta-analysis suggests that CYP1B1 Arg48Gly, Ala119Ser and Asn453Ser polymorphisms are not associated with breast cancer risk. Studies on Chinese populations are needed, to elucidate race-specific effects on East Asian populations, if any. © Springer Science+Business Media, LLC. 2010

XRCC3 Thr241Met polymorphism and breast cancer risk: A meta-analysis

XRCC3 (X-ray repair complementing defective repair in Chinese hamster cells 3) is a member of the RecA/ Rad51-related protein family that participates in homologous recombination, maintaining chromosome stability and participating in DNA repair. Attention has been drawn upon the association of XRCC3 Thr241Met polymorphism with breast cancer risk. The present meta-analysis aims to examine whether XRCC3 Thr241Met polymorphism status is associated with breast cancer risk. Apart from the overall meta-analysis, separate analyses were performed on Chinese and non-Chinese populations, in order to investigate race-specific effects. Eligible articles were identified by a search of MEDLINE bibliographical database for the period up to August 2009. Twenty case-control studies on nonChinese subjects (19,575 cases and 21,125 controls) and three case-control studies on Chinese subjects (1,216 cases and 1,112 controls) were eligible. Pooled odds ratios (OR) were appropriately derived from fixed-effects or randomeffects models. At the overall analysis, the T allele was associated with elevated breast cancer risk mainly following a recessive model (pooled OR = 1.064,95% CI: 1.007-1.124, fixed effects), given that the effect was more pronounced in homozygous carriers (pooled OR = 1.073,95% CI: 1.010-1.140, fixed effects). The association seemed confined in non-Chinese populations, once again following a recessive model (pooled OR = 1.072, 95% CI: 1.014-1.133, fixed effects). Concerning Chinese populations, no consistent results were demonstrated. In conclusion, the XRCC3 Thr241 Met T allele seems associated with elevated breast cancer risk in non-Chinese subjects. The need for additional studies on Chinese populations seems warranted. © Springer Science+Business Media, LLC. 2009

GSTM1, GSTT1, GSTP1, GSTA1 and colorectal cancer risk: A comprehensive meta-analysis

Glutathione S-transferases (GSTs) catalyse reactions between glutathione and lipophilic compounds with electrophilic centres, leading to neutralisation of toxic compounds, xenobiotics and products of oxidative stress. Controversy exists about whether GST polymorphisms (GSTM1 null/present genotype, GSTT1 null/present genotype, GSTP1 Ile105Val and GSTA1*A/*B) represent risk factors for colorectal cancer. This meta-analysis aims to examine the associations between the above-mentioned polymorphisms and colorectal cancer risk. Forty-four studies were eligible for GSTM1 (11,998 colorectal cancer cases, 17,552 controls), 34 studies for GSTT1 (8596 cases, 13,589 controls), 19 studies for GSTP1 (5421 cases, 7671 controls) and four studies for GSTA1 polymorphism (1648 cases, 2039 controls). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models. Separate analyses were conducted on Caucasian and Chinese populations. Where appropriate, sensitivity analysis concerning the deviation of genotype frequencies in controls from the Hardy-Weinberg equilibrium was performed. GSTM1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR = 1.150, 95% confidence interval (CI): 1.060-1.248, random effects); no significant association was detected for Chinese subjects (pooled OR = 1.025, 95% CI: 0.903-1.163, fixed effects). Similarly, GSTT1 null allele carriers exhibited increased colorectal cancer risk in Caucasian populations (pooled OR = 1.312, 95% CI: 1.119-1.538, random effects); the association in Chinese subjects was not significant (pooled OR = 1.068, 95% CI: 0.788-1.449, random effects). Concerning GSTP1 Ile105Val no significant associations were demonstrated in either race. GSTA1*A/*B polymorphism was not associated with colorectal cancer risk. GSTM1 and GSTT1 null genotypes confer additional risk for colorectal cancer in Caucasian populations. © 2010 Elsevier Ltd. All rights reserved